Kobayashi Hiroshi, Yamada Yoshihiko, Kanayama Seiji, Furukawa Naoto, Noguchi Taketoshi, Haruta Shoji, Yoshida Shozo, Sakata Mariko, Sado Toshiyuki, Oi Hidekazu
Department of Obstetrics and Gynecology, Nara Medical University, Japan.
Int J Gynecol Cancer. 2009 Apr;19(3):471-9. doi: 10.1111/IGC.0b013e3181a19eca.
Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC.
This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology.
Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1beta (HNF-1beta) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1beta-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents.
This review summarizes recent advances in the HNF-1beta and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.
卵巢透明细胞癌（CCC）具有许多特征，使其有别于其他上皮性卵巢癌（EOC），这是由于其独特的组织学和生物学特性、常与子宫内膜异位病变同时存在以及具有高度化疗耐药性，导致预后极差。在日本，CCC的发病率一直在稳步上升。它们约占所有EOC的20%。了解CCC的发生机制并阐明其发病机制和病理生理学，对于CCC的预防和有效治疗至关重要。
本文综述了关于子宫内膜异位症相关EOC的生物学、发病机制和病理生理学研究的英文文献。在子宫内膜异位症和CCC生物学的背景下讨论了一些数据。
基于全基因组表达分析技术的最新研究指出，肝细胞核因子-1β（HNF-1β）在子宫内膜异位症和CCC中特异性表达，这表明在子宫内膜异位症中发生了向透明细胞谱系的早期分化。将讨论CCC的HNF-1β依赖性途径，这些途径为细胞凋亡和糖原合成的调控以及CCC对抗癌药物的耐药性提供了新的见解。
本综述总结了HNF-1β及其靶基因的最新进展；在理解CCC的致癌作用、发病机制和病理生理学方面面临的潜在挑战；并提出了一种可能的新模型。
